An α‐Helix‐Mimicking 12,13‐Helix: Designed α/β/γ‐Foldamers as Selective Inhibitors of Protein–Protein Interactions
Grison, Claire M.
Miles, Jennifer A.
Wilson, Andrew J.
Aitken, David J.
- Publisher: John Wiley and Sons Inc.
Angewandte Chemie (International Ed. in English)
(issn: 1433-7851, vol:
protein–protein interactions | inhibitors | Communications | α-helix mimetics | peptidomimetics | Communication | foldamers
Abstract A major current challenge in bioorganic chemistry is the identification of effective mimics of protein secondary structures that act as inhibitors of protein–protein interactions (PPIs). In this work, trans‐2‐aminocyclobutanecarboxylic acid (tACBC) was used as the key β‐amino acid component in the design of α/β/γ‐peptides to structurally mimic a native α‐helix. Suitably functionalized α/β/γ‐peptides assume an α‐helix‐mimicking 12,13‐helix conformation in solution, exhibit enhanced proteolytic stability in comparison to the wild‐type α‐peptide parent sequence from which they are derived, and act as selective inhibitors of the p53/hDM2 interaction.